tbuckley/cabot-search huggingface dataset:
Abstract 15353: Identifying Different Clinical Phenotypes in Peripartum Cardiomyopathy by Latent Class Analysis
Authors: Olamide Oyenubi, Patrick Benjamin, Marvyn Allen G Chan, Bisrat Teweldemedhin, David Gruen, Daniel Pomerantz, Stephen Jesmajian
Journal: Circulation (2022)

Introduction: Peripartum cardiomyopathy (PPCM) is a heterogeneous disorder whose pathophysiology remains poorly understood. To better understand the heterogeneity of PPCM, we used latent class analysis (LCA) to explore the different clinical phenotypes in a large sample of PPCM patients. Methods: Using the National Inpatient Sample (NIS) database, we identified 917 patients admitted to hospitals in 2017-2019 with a primary diagnosis of PPCM. We performed LCA based on 8 risk factors: age (&lt; 30 vs &gt; 30), race (African American (AA) vs non-AA), hypertension in pregnancy (HIP) (preeclampsia, gestational hypertension, or chronic hypertension), diabetes mellitus (DM), obesity, tobacco use, cannabis use, and psychiatric disorders (anxiety, depressive, bipolar, or schizophrenia spectrum disorders). We then compared in-hospital outcomes among the different clusters identified by LCA. Data were analyzed using Stata version 17 for descriptive analysis and Mplus version 8.8 for LCA. Results: Four patient clusters were identified. C1 (n=471, 51.4%) had no AA or cannabis users and members had the lowest probability of having HIP (0.387), DM (0.27), and obesity (0.17). C2 (n=328, 35.8%) were all AA who did not use cannabis and had the lowest probability of using tobacco (0.076), and having psychiatric disorders (0.084). C3 (n=31, 3.4%) was the youngest group all of whom used tobacco and cannabis and had the largest probability of having psychiatric disorders (0.484). On the other hand, C4 (n=87, 9.5%) was the oldest group none of whom used cannabis but members had the highest probability being obese (0.664), having HIP (0.825), and DM (0.642). Among all clusters, C3 had the lowest in-hospital mortality (0.0%) and hospital charges ($57,357). C4 had the highest in-hospital mortality 1.1% and longest hospital length of stay (5.4 ± 7.0 days). Conclusions: Using LCA, we identified four clinically distinct classes PPCM with varying in-hospital outcomes. These may reflect different additional underlying mechanisms in PPCM. Our findings may help identify treatment targets and patient selection for future clinical trials.
Abstract 14587: Dysregulation of Vascular Autophagy by Overexpression of p25/CDK5 is Associated With Vascular Senescence
Authors: David G Mondaca Ruff, Ji Yong Kim, Sandeep Singh, Yu Wang
Journal: Circulation (2022)

Introduction: Cardiovascular diseases are the main causes of death worldwide. These diseases are often associated with cardiovascular aging. Autophagy is a degradative cellular process that has been implicated in aging regulation. Cyclin-dependent kinase 5 (CDK5), which is normally activated by its regulatory subunit p25, has been implicated in several diseases. However, the role of p25/CDK5 signaling pathway in cardiovascular diseases and autophagy have not been fully understood. Hypothesis: Upregulation of vascular p25/CDK5 signaling pathway modifies autophagy induction and participates in vascular senescence. Methods: Selective overexpression of p25 (CDK5 activator) in the vascular endothelium was generated in a transgenic mouse model (EC-p25). Then, aortas from 30-weeks old EC-p25 and control mice were collected. Vascular senescence was evaluated with senescence-associated β-galactosidase (SA-β-gal) staining. Protein levels were measured by Western blotting. Primary porcine aortic endothelial cells (PAECs) were transfected with pcDNA, p25 and CDK5. Autophagy activity, autophagic flux, cell death, and senescence were evaluated. A p-value of p&lt;0.05 was considered as statistically significant. Results: EC-p25 mice exhibited increased SA-β-gal staining compared to the Control mice suggesting accelerated aging in the aorta. EC-p25 mice showed increased levels of autophagy compared to the Control mice. On the other hand, overexpression of CDK5 increased cell death, endothelial senescence, autophagy and proteins involved in autophagy induction in PAECs. Conclusion: Accelerated premature vascular aging induced by selective overexpression of the p25/CDK5 signaling pathway in the vascular endothelium may be associated with increased vascular senescence in the aorta by modifying autophagy activity and induction process.
Abstract 14439: Using Augmented Mean Arterial Pressure to Assess Post-Transcatheter Aortic Valve Replacement Mortality
Authors: Chiehju Chao, Pradyumna Agasthi, Amith Reddy Seri, Timothy Barry, Anusha Shanbhag, Yuxiang Wang, Mackram F Eleid, Floyd D Fortuin, John Sweeney, Peter Pollak, Abdallah El Sabbagh, Steven Lester, william freeman, Tasneem Z Naqvi, David R Holmes, Chris P Appleton, Reza Arsanjani
Journal: Circulation (2022)

Introduction: Post-transcatheter aortic valve replacement (TAVR) outcome of patients is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo-parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure parameters (AugMAP)) derived from blood pressure and aortic valve gradient ( Figure 1 ). Methods: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between January 1, 2012, and June 30, 2017, were identified to retrieve baseline clinical, echocardiographic, and mortality data. The median of AugSBP and AugMAP were used to stratify patients in Kaplan-Meier analysis. Results: The final cohort contained 974 patients with a mean age of 81.4±8.3 years old, and 56.6% were male. The mean Society of Thoracic Surgeons risk score was 8.2±5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Detailed characteristics are summarized in Table 1. AugMAP1 &lt; 102.5 mmHg (median) was associated with a 3-fold risk of all-cause mortality post-TAVR at 1 year (hazard ratio 3.0, 95%confidence interval 2.0-4.5, p&lt;0.0001)( Figure 1 ). Conclusions: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis.
Abstract 15290: Hypertension in Black and White Breast Cancer Survivors: NCT02992730
Authors: Vanessa B Sheppard, Arnethea L Sutton, Alexander R Lucas, Robert L Franco, Kerryn Reding, Youngdeok Kim, Richard Cheng, Matthew B Wells, William G Hundley
Journal: Circulation (2022)

Introduction: Hypertension (HTN) may increase the risk of cardiovascular (CV) events among breast cancer (BC) survivors, particularly in Black women. Limited information is available about factors associated with the presence of HTN at the time of BC diagnosis among Black versus White women. Methods: In a secondary analysis of data from a longitudinal cohort of Black and White women diagnosed with hormone receptor positive (HR+) BC, post initiation of adjuvant endocrine therapy (AET), medical records were used to determine HTN status and other clinical factors (stage, AET type, CV comorbidities). In the same cohort, psychosocial and quality of life data were collected via surveys. Logistic regression models evaluated factors associated with increased odds of HTN at baseline. Results: Women with BC (n=243) were mostly White (66.7%), mean (SD) aged 61.6 (10.9) years, with borderline obesity (BMI: 29.9 (6.6)). Comorbidities and tamoxifen use were reported by 40.7% and 28.4% of women, respectively. HTN was present in 140 (57.6%) women (38% Black, 62% White). Relative to their White counterparts, Black women with HTN were significantly younger, (61.5 vs. 67.5 years of age, p&lt; 0.01) more overweight (BMI, 32.8 vs 29.3, p =&lt;.01), received chemotherapy more frequently (44.4% vs 22.1%, p &lt;0.01), were more likely to have experienced discrimination (35.2% vs 7%, p &lt;0.01) and more often to possess CV comorbidities (61.1% vs 37.2%, p &lt;0.01). Multivariable logistic regression showed that the odds of having HTN increased significantly with age by 10% per year (OR: 1.10, 95% CI: 1.06-1.14; p&lt;.0001), with Black women having a 2-fold greater risk of having HTN (OR: 2.02, 1.02-4.03; p=.044) than White women. Additionally, a 1-unit increase in BMI was associated with 6% higher odds of having HTN (OR: 1.06, 95% CI: 1.03-1.11; p=0.0390) while Tamoxifen use, presence of CV comorbidities and worse social well-being were not associated with more frequent HTN in women with BC. Conclusions: A high proportion of women diagnosed with HR+ BC have HTN with Black vs White women experiencing more HTN. These results raise the possibility that Black women with BC may benefit from focused HTN management strategies to reduce potential CV events.
Abstract 15341: Persistent Fifth Arch as an Aortopulmonary Connection in a Case of Tetralogy of Fallot
Authors: Lianela C Negron Garcia, Hannah Fraint, Philip C Spevak, William J Ravekes
Journal: Circulation (2022)

Persistent fifth aortic arch is a heterogeneous vascular anomaly with variable anatomical presentations and physiological consequences. This unusual embryological remnant represents a management challenge, particularly in critical right sided obstructive heart lesions where accurate delineation of sources of pulmonary blood flow is essential. This is a newborn 2 kg premature male born at 34 weeks of gestation with prenatally diagnosed tetralogy of Fallot. Post-natal echocardiogram confirmed diagnosis with evidence of moderate-to-severe pulmonary stenosis, restrictive ventricular septal defect, and a right aortic arch. CT angiogram ordered to delineate the head and neck vessel anatomy showed an exceedingly rare finding of an isolated connection of the left subclavian artery (LSCA) to the main pulmonary artery (MPA) via a left sided ductus arteriosus. Blood flowed from the common carotid arteries, through the circle of Willis, and, in a retrograde direction, into the LSCA. Prostaglandin E was initiated due to concern for ductal dependent pulmonary blood flow, but after clinical observation it was discontinued without subsequent onset of cyanosis. Repeat echocardiograms were reassuring in showing persistence of the left ductus arteriosus. The patient was discharged home at 5 weeks-old and at 4 months-old he underwent complete repair after developing progressive desaturations and worsening sub-valvar and valvar pulmonary stenosis. The surgical repair included ventricular septal defect closure, transannular patch, extensive right ventricular myomectomy and reimplantation of LSCA onto the left common carotid artery. The post-operative course was uncomplicated. This rare case of persistent fifth aortic arch with retrograde flow to the LSCA demonstrates the complementary roles of noninvasive imaging modalities in guiding medical therapy and surgical management. This unusual blood flow pattern and initial concern for duct dependent pulmonary blood flow complicated early management, but a conservative approach with repeat imaging allowed for eventual complete repair.
Abstract 185: Dual Processing In Surrogate Decision Makers Of Out Of Hospital Cardiac Arrest Patients: A Secondary Qualitative Analysis
Authors: Alex Presciutti, Bonnie Siry-Bove, Laura D Scherer, Bethany Kwan, Dan D Matlock, Stacie Daugherty, Edward P Havranek, Sarah M Perman
Journal: Circulation (2022)

Introduction: Out-of-hospital cardiac arrest (OHCA) is an unexpected event that frequently renders patients incapacitated therefore requiring a surrogate decision maker (SDM) to act as a proxy. When exercising judgement under uncertainty, people engage in one of two cognitive processing styles (i.e., dual processing): “fast” processing - automatic and intuitive or “slow” processing - deliberative and rational. Understanding which style(s) SDMs use in making decisions for post-arrest patients is critical to ensuring that (1) patients’ wishes are respected and (2) evidence-based neuro-prognostication is supported. Methods: We conducted a secondary analysis of semi-structured interviews with SDMs for OHCA patients. Potential subjects were contacted 30 days after discharge/death. The interviews were recorded and transcribed verbatim. Two investigators thematically coded the transcripts. We conducted secondary coding to specifically explore cognitive processing styles used by SDMs. Results: Over 5-months, 34 SDMS were approached and 12 SDMs agreed to be interviewed. SDMs were spouses/partners (5), adult children (3), parent (1) and siblings (3). Within this sample, 66.7% (8/12) of SDMs decided to withdraw life sustaining therapy or discontinue resuscitative efforts for the patient. Our secondary coding yielded variation in cognitive processing styles, with SDMs describing both fast and slow styles. SDMs who employed “fast” cognitive processing described (1) making their decision based on group consensus, (2) employing an affect heuristic (deciding based on “gut feeling” or temporary emotional state), (3) employing an availability heuristic (deciding based on examples of other patients or scenarios that immediately come to mind), and (4) deciding based on providers’ opinions without consulting other sources. SDMs who utilized “slow” cognitive processing described (1) focusing on the patient’s wishes when deciding and (2) gathering information to make an informed decision. Conclusions: SDMs utilized “fast” and “slow” cognitive processing approaches to decision making for OHCA patients. Future study should explore the relationship between SDMs’ cognitive processing styles and their decisions for post-arrest care.
Abstract 15380: Cardiac Localized Polycystin 2 is Required for Natriuretic Peptide Production and Its Absence is a Main Driver of Hypertension
Authors: Brandon Lantonio, Ivana Y Kuo
Journal: Circulation (2022)

Introduction: Autosomal Dominant Polycystic Kidney Disease (ADPKD) occurs in 1:1000 births and causes renal cysts and loss of renal function. However, cardiovascular complications are the most common cause of mortality in ADPKD patients and hypertension affects 70% of patients before decline in renal function. ADPKD arises from mutations in PKD1 and PKD2, encoding Polycystin 1 and Polycystin 2 (PC2) respectively. PC2 forms a nonselective cation pore channel that conducts calcium. Heterozygous mice for Pkd2 have attenuated natriuretic peptide (NP) responses. The NPs, ANP and BNP, are regulators of euvolemia via renal excretion of sodium following cardiac atrial and ventricular stretch, thought to be a calcium activated process. We hypothesized cardiac PC2 contributes to NP production and loss of PC2 induces hypertension without renal involvement. Methods: Cardiomyocyte inducible PC2 KO (PC2 cKO) mice were generated by crossing Pkd2 floxed mice with αMHC-MerCreMer mice. Cardiomyocyte Cre expression was induced by tamoxifen diet at 6 weeks. Mice were aged to 7 months and had intra-aortic blood pressure monitoring or left ventricular tissue collection for quantitative PCR (qPCR) analysis. Male and female mice (n=4-9) were used and analyzed separately by Student’s t-Test, with a p &lt;0.05 considered statistically significant. Results: PC2 cKO mice had elevated diurnal blood pressure (160/110mmHg) without renal cysts. Comparisons were made to age-matched controls. All reported genes were affected in males and females, with only female data reported (Mean ± SEM). qPCR analysis showed that PC2 cKO mice had a ~50% decrease in Nppa (WT: 1± 0.2 KO: 0.6 ± 0.1) and Nppb (WT: 1 ± 0.1 KO: 0.5 ± 0.2) mRNA, genes encoding ANP and BNP respectively. There was a ~60% reduction in Pcsk6 (WT: 1 ± 0.1, KO: 0.4 ± 0.1) mRNA in PC2 cKO mice, a gene encoding a protease necessary for Corin activity, regulating ANP. Cgb mRNA was abolished (WT: 1 ± 0.2, KO: 0.03 ± 0.01) in PC2 cKO mice, encoding Chromogranin B, a regulator of NF-κB mediated production of Nppb mRNA and ANP-containing vesicles. Conclusion: We conclude loss of PC2 in cardiomyocytes leads to a hypertensive phenotype which may arise from a calcium-dependent multi-component dysfunction of cardiomyocyte NP production.
Abstract 15674: Utilization Rates of Follow-Up Testing With Pyp Scan and Cardiac Mri, and Clinical and Demographic Determinants of Their Use Among Patients With Echocardiographic Features of Cardiac Amyloidosis: A Population-Based Case Control Study
Authors: Nathaniel Fessehaie, HIlary Bediako, Michael Levin, Michael Kallan, Howard Julien, Lauren A Eberly
Journal: Circulation (2022)

Introduction: Cardiac amyloidosis (CA) is an underdiagnosed cause of heart failure. Echocardiography provides an excellent screening tool for cardiac amyloidosis. For patients with echocardiographic findings suggestive of cardiac amyloidosis, it is unknown how frequently follow-up imaging such as 99mTc PYP-scan or cardiac MRI is obtained. Diagnosis rates after a suggestive echocardiogram as well as disparities in rates of follow-up imaging and subsequent CA diagnosis are also unknown. Methods: We extracted all index cardiac echocardiograms at our institutions of adult patients that were suggestive of a possible diagnosis of CA, which was defined as: moderate or worse left ventricular concentric hypertrophy plus grade II or grade III diastolic dysfunction or diastology could not be determined due to arrhythmia in those with atrial fibrillation. Patients with known diagnosis of amyloidosis were excluded. We determined which patients underwent further testing with 99m Tc-PYP scan or cardiac MRI. We performed a population based case control study in which we compared clinical and demographic factors between those who underwent follow-up testing with either PYP scan or cardiac MRI (cases) vs those who did not (controls). Results: Of 1348 echoes that met inclusion criteria, only 110 (8.2%) underwent PYP scan or cardiac MRI. Of those, 10.0 (11%) patients ultimately were diagnosed with CA. Between cases and controls, there was no difference in age, gender, or race/ethnicity. There were no differences in rates of HFrEF or HFpEF between cases and controls. Cases had lower rates of CKD (27% vs. 40%, p=0.01) and ESRD (8.2% vs 15%, p=0.03) and had higher rates of carpal tunnel disease (12% vs. 6%), p&lt;0.05). The rates of cardiologist ordered echocardiograms were similar between cases and controls. In terms of echocardiogram parameters, there were higher rates of grade III diastolic dysfunction (36.7% vs 20.4%, p=0.002) and more frequent rates of severe hypertrophy (36.7% vs. 21.7% p=,0.004)) among cases vs. controls. Conclusions: Among patients with echocardiographic features suggestive of CA, follow-up testing with 99m Tc -PYP scans and Cardiac MRI, and subsequent diagnosis with CA remain low.
Abstract 14647: Effects of an App-Based Exercise Intervention Program on Exercise Capacity for Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis
Authors: Minjeong An, Yeonhu Lee
Journal: Circulation (2022)

Introduction: Mobile-based healthcare is considered a strategy that can overcome time and space constraints and increase the participation rate of a heart health program; however, a review of the elements of exercise prescription, such as frequency, intensity, time, and type (FITT), has been insufficient. Therefore, a systematic review and meta-analysis were performed to identify the FITT elements of an app-based exercise heart health intervention that was effective in improving the exercise capacity of patients with Acute Coronary Syndrome (ACS). Methods: A literature search was conducted for papers published up to November 2021. We searched for randomized controlled trials (RCTs) evaluating the effectiveness of an exercise-based heart health program using a smartphone app for adult inpatients initially diagnosed with ACS, who received primary percutaneous coronary intervention or medication treatment. With the help of our librarians, we searched MEDLINE, EMBASE, and Cochrane CENTRAL. Literature selection, bias evaluation, and data collection were independently performed by two researchers. Cochrane Risk of Bias 2 was used to evaluate the quality of literature; the level of evidence was evaluated using GRADE, and CMA Version 3.0 was used for the meta-analysis. Effect size for exercise capacity was calculated using standardized mean difference. Results: Seven RCTs were identified. The study results suggested that using an app-based exercise heart health program was effective in improving the exercise capacity of patients in Phase III of cardiac rehabilitation post-ACS. As a confirmed exercise prescription factor, the app was found to be effective in improving exercise capacity when aerobic exercise was performed for approximately 30 minutes at least three to five times a week. The effect size for exercise capacity was 0.42 (95% CI, 0.24-0.60; I 2 , 45.00; p &lt;.001). App-based exercise interventions was confirmed to be effective in improving exercise capacity compared to general heart health interventions. Conclusions: An app-based exercise heart health intervention is safe and effective in improving exercise capacity and encouraging post-ACS patients who are in Phase III of cardiac rehabilitation to start exercise after hospital discharge.
Abstract 15356: Serial Evaluation of Chemotherapy-Induced Vascular Toxicity in a Rat Model Using <sup>18</sup> F-FDG PET/CT Imaging
Authors: Mahboubeh Nabavinia, Maren Beall, Eleanor T Rimmerman, Kumudha Musini, Donny Deep, Mitchel R Stacy
Journal: Circulation (2022)

Introduction: Cancer treatment with chemotherapeutics can lead to off-target effects on the vasculature. Fluorine-18 ( 18 F)-fluorodeoxyglucose (FDG) PET/CT imaging is standard of care for staging and monitoring of numerous cancers and may offer a tool for assessing vascular toxicity. We hypothesized that PET/CT imaging could quantify changes in chemotherapy-induced arterial inflammation. Thus, we sought to validate PET/CT imaging as a tool for assessing vascular toxicity in a rat model using in vivo imaging and post-mortem analyses. Methods: Male Wistar rats (n = 11 total) were divided into a control group that received twice weekly IV saline (n=5; 1 ml/kg) or a group that received twice weekly IV doxorubicin (n=6; 1 mg/kg) for 2.5 weeks (i.e., 7 mg/kg cumulative dose). Rats underwent 18 F-FDG microPET/CT imaging of the abdominal aorta (AA) at 3 time points (baseline, after 4 mg/kg dosing, and after 7 mg/kg cumulative dose) to quantify serial changes in arterial inflammation, expressed as changes in the maximum standard uptake value (SUV max ). Following terminal imaging, AA tissue was harvested and cut into 3 mm sections for gamma counting of 18 F-FDG uptake, hematoxylin and eosin morphological staining, and immunohistochemistry of macrophage expression. Results: In vivo image analyses demonstrated that 18 F-FDG uptake remained unchanged for the control group during the treatment period, but significantly increased from baseline levels in the doxorubicin-treated group after 4 mg/kg (p=0.0007) and 7 mg/kg (p=0.001) cumulative dosing. In vivo image analyses were confirmed by post-mortem gamma counting of 18 F-FDG uptake in anatomically-matched AA tissue samples. Histological analyses revealed increased levels of macrophage expression in sections with increased 18 F-FDG uptake identified by in vivo and ex vivo analyses. Conclusions: 18 F-FDG PET/CT imaging non-invasively quantifies serial changes in chemotherapy-induced arterial toxicity that are at least partially mediated by increased macrophage activity. Routine assessment of 18 F-FDG uptake on PET/CT imaging studies during cancer treatment could provide a translatable approach for characterizing the time course of vascular toxicity associated with various chemotherapeutics.